Capivasertib Combo Significantly Improves rPFS in PTEN-Deficient HSPC

The safety profile of capivasertib plus abiraterone/ADT in the CAPItello-281 trial was comparable with prior reports of each individual agent. Investigators will present additional data at a future medical meeting and share their findings with global regulatory authorities.

Combining capivasertib (Truqap) with abiraterone acetate (Zytiga) and androgen deprivation therapy (ADT) produced a clinically meaningful and statistically significant radiographic progression-free survival (rPFS) improvement vs placebo plus abiraterone/ADT among those with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer (HSPC), according to findings from the phase 3 CAPItello-281 trial (NCT04493853).¹

Results also showed an early trend towards improved overall survival (OS) with the capivasertib-based combination, although these data were not yet mature at the time of analysis. Investigators will continue with the trial as planned to further evaluate OS.

The safety profile of capivasertib plus abiraterone/ADT in the CAPItello-281 trial was comparable with prior reports of each individual agent. Investigators will present additional data at a future medical meeting and share their findings with global regulatory authorities.

“Patients with this aggressive form of prostate cancer with tumor PTEN deficiency currently [have] a particularly poor prognosis, and there is an urgent need for new treatments that improve upon current therapies,” principal trial investigator Karim Fizazi, MD, PhD, of Institut Gustave Roussy and University of Paris Saclay in Villejuif, France, stated in a press release on these findings.¹ “The results seen with capivasertib in combination with abiraterone plus prednisone and ADT in the CAPItello-281 trial represent a step forward for these patients.”

Investigators of the double-blind, randomized phase 3 CAPItello-281 trial assessed the efficacy and safety of capivasertib plus abiraterone/ADT vs placebo plus abiraterone/ADT among 1012 adult patients with PTEN-deficient de novo metastatic HSPC. Patients were randomly assigned 1:1 to receive capivasertib at 400 mg twice daily or matched placebo on days 1 to 4 of each 28-day cycle in combination with abiraterone at 1000 mg daily.²

The trial’s primary end point was rPFS, defined as the time from randomization to death or radiographic progression per RECIST v1.1 criteria for soft tissue and/or Prostate Cancer Working Group 3 guidelines for the bone. Secondary end points included OS, time to start of first subsequent therapy or death, symptomatic skeletal event-free survival, time to pain progression, time to prostate-specific antigen progression, time to castration resistance, PFS after next-line treatment, and the plasma concentration of capivasertib before and after dosing.

Investigators also assessed fatigue per the Brief Fatigue Inventory, overall pain severity and pain interference based on the Brief Pain Inventory-Short Form questionnaire, and disease-related symptoms and health-related quality of life per the Functional Assessment of Cancer Therapy – Prostate Cancer questionnaire.

Patients 18 years and older with asymptomatic or mildly symptomatic, histologically confirmed de novo hormone-sensitive prostate adenocarcinoma without small cell tumors diagnosed within 180 days of randomization were eligible for enrollment on the trial. Other requirements for study entry included having metastatic disease, an ECOG or World Health Organization performance status of 0 to 1, and valid PTEN deficiency per centralized testing.

Those with prior radical prostatectomy or definitive radiotherapy administered with therapeutic intent for prostate cancer or major surgery within 4 weeks of beginning study treatment were ineligible for enrollment on the trial.

“These results show, for the first time, that adding an AKT inhibitor to a standard-of-care therapy can provide benefit to patients with a biomarker of PTEN-deficient metastatic [HSPC]. By targeting a key driver of the disease, we have been able to improve upon current therapies and demonstrate the potential role of this combination in an area of critical unmet need,” Susan Galbraith, executive vice president of Oncology Research and Development at AstraZeneca, the developer of capivasertib, concluded.¹

References

1. TRUQAP® (capivasertib) combination in PTEN-deficient metastatic hormone-sensitive prostate cancer demonstrated statistically significant and clinically meaningful improvement in radiographic progression-free survival in CAPItello-281 phase III trial. News release. AstraZeneca. November 25, 2024. Accessed November 25, 2024. https://tinyurl.com/tnwmuwpk
2. Capivasertib+abiraterone as treatment for patients with metastatic hormone-sensitive prostate cancer and PTEN deficiency (CAPItello-281). ClinicalTrials.gov. Updated July 23, 2024. Accessed November 25, 2024. https://tinyurl.com/yckbsxhc